An existing partner with two other deals jumped aboard Ambrx Inc.'s site-specific, antibody drug conjugate (ADC) bandwagon, as Bristol-Myers Squibb Co. provided $15 million up front plus funding for discovery and research, as well as milestone payments of that could total $97 million per oncology product emerging from the collaboration.
"I think it is based on the relationship we've built with BMS, but this is a different franchise area, a different portion of our technology platform," said Simon Allen, chief business officer of San Diego-based Ambrx.
The firm has deals with BMS dating from 2011. Both involve Ambrx's protein medicinal chemistry technology, one targeting fibroblast growth factor 21 for Type II diabetes and the other focused on the relaxin hormone for the treatment of heart failure. BMS is developing both. (See BioWorld Today, Sept. 23, 2011.)
The compounds in these earlier deals were developed using Ambrx's ReCODE (reconstituting chemically orthogonal directed engineering) technology to improve existing protein drugs by genetically engineering them with amino-acid building blocks beyond the 20 naturally occurring amino acids. The resulting products are designed to have better efficacy and safety than existing protein-based drugs.
"As you might imagine, we've been discussing ADCs with BMS for some time," Allen said. "It's not as though we've just started conversations with them. We've been able to show them our technology. We've shared data. They've generated data in their own hands with our ADCs, and that process typically leads to these types of collaborations."
Ambrx has had little trouble wooing big pharma in general. Tokyo-based Astellas Pharma Inc. agreed last month to an oncology-focused discovery and development collaboration in ADCs, with $15 million up front and up to $285 million in potential near- and long-term research, development, regulatory and sales-based milestones for an undisclosed number of ADC targets in oncology. (See BioWorld Today, April 8, 2012.)
Last year, Ambrx signed a potential $303 million agreement with Whitehouse Station, N.J.-based Merck & Co. Inc. to design and develop rationally optimized biologic drug conjugates. (See BioWorld Today, June 19, 2012.)
On its own, Ambrx is developing ARX201, a long-acting growth hormone from the ReCODE part of the platform that has finished Phase IIb trials. "We're gearing up for [Phase III] clinical supply" with the HGH candidate, while shopping for a partner, Allen told BioWorld Today.
ADCs are hot. Companies such as Seattle Genetics Inc. and ImmunoGen Inc. have proven the worth of the approach in cancer: Bothell, Wash.-based Seattle Genetics won approval in 2011 for CD30-targeting ADC Adcetris (brentuximab vedotin). In February of this year, the FDA gave its nod to T-DM1, branded Kadcyla, which pairs Roche AG's Herceptin (trastuzumab) with ImmunoGen Inc.'s DM1 maytansinoid cell-killing agent in HER2-positive metastatic breast cancer. (See BioWorld Today, Aug. 22, 2011, and Feb. 25, 2013.)
"We've been working on ADCs for a number of years, well before the approval of Adcetris and, more recently, Kadcyla," Allen said. "The tipping point, in our minds, has been the success of those molecules, which we call conventional conjugation or non-specific conjugation. When we realized the benefits of site-specific conjugation – which is really the essence of what Ambrx does – we focused our efforts, probably about three years ago."
Recent interest in ADCs, "which a lot of people are seeing with the success of those [approved] products in the market, as well as the type of transactions that we're announcing today, comes as no surprise to us but it's really only over the last year or so that it's come to the forefront of peoples' attention."
Among the other ADC players is Celldex Therapeutics Inc., which in February raised $90 million plus $12.7 million for overallotments in a public offering to advance rindopepimut, its immunotherapy targeting epidermal growth factor variant III, in a registration study in front-line glioblastoma multiforme, and CDX-011 (glembatamumab vedotin), a fully human monoclonal ADC targeting glycoprotein NMB in Phase II development in breast cancer. (See BioWorld Today, Feb. 7, 2013.)
Sutro Biopharma Inc., of San Francisco, in December 2012 inked a potential $500 million deal with Summit, N.J.-based Celgene Corp. that includes two undisclosed targets against which ADCs and bispecific antibodies will be directed plus the manufacturing of a Celgene-owned antibody to explore Sutro's platform further. (See BioWorld Today, Dec. 19, 2012.)
An overseas, ADC-busy firm is UK-based Oxford BioTherapeutics Ltd., which has landed what it called a "transformational" deal with Menarini, in which the Italian pharma company invested €800 million (then US$1 billion) in a portfolio of five antibody and ADC drugs discovered by OBT. (See BioWorld Today, October 30, 2012.)